Dipeptide Ligands of TSPO

Our own investigations of the synthesis and pharmacological properties of dipeptide ligands of the translocator protein (TSPO) are reviewed. The compounds were designed based on the original chemical and pharmacological strategy of designing short peptides that are similar to known drugs. Two series of TSPO dipeptide ligands, substituted tryptophanyl isoleucines and substituted tryptophanyl leucines, were designed and synthesized. Data for their anxiolytic activities, the proposed molecular mechanisms of action of the lead compounds, and the structure—activity (anxiolytic) relationship of their analogs are presented. The pharmacophore elements necessary for the manifestation of the anxiolytic effects of these compounds are described. A hypothesis about the structure of the putative endogenous TSPO ligand is formulated.